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甲泼尼龙和卤泛群对预防放射性治疗后食管和咽下部纤维化的作用。

The effects of methylprednisolone and halofuginone on preventing esophageal and hypopharyngeal fibrosis in delivered radiotherapy.

机构信息

Department of Otorhinolaryngology, Medical Faculty, Firat University, 23119, Elazig, Turkey.

出版信息

Eur Arch Otorhinolaryngol. 2010 Sep;267(9):1429-35. doi: 10.1007/s00405-010-1242-y. Epub 2010 Apr 3.

DOI:10.1007/s00405-010-1242-y
PMID:20364346
Abstract

In this study, we assessed the effects of halofuginone and methylprednisolone on hypopharyngeal and esophageal stricture that can develop following radiation to the head and neck of rats. Rats were divided into four groups randomly and 18 Gy radiation was given to the head and neck regions of all rats except the control group. Group 1 (Control Group): No radiation or drugs were administered. Group 2 (Radiation Group): only radiation was applied without any drugs. Group 3 (Halofuginone Group): halofuginone 100 microg/kg per day was given intraperitoneally. Group 4 (Methylprednisolone Group): methylprednisolone 1 mg/kg per day was administered intramuscularly. In all groups, 90 days after application of radiation, sections of the proximal esophagus and hypopharynx were examined for fibrosis, fibroblast proliferation, vascularization, epithelial atypia, necrosis, polymorphonuclear leukocytes, mononuclear cells, and stenosis index by light microscope and the hydroxyproline levels were assessed biochemically. Fibrosis, epithelial atypia and hydroxyproline levels were found to be significantly higher in the radiation group compared to the control group (P < 0.05). We did not observe fibrosis in either the halofuginone or the control groups. Fibrosis was also significantly lower in the methylprednisolone group than the radiation group (P < 0.05). The differences of the stenosis index scores between the groups were not statistically significant (P < 0.05). Vascularization was similar in all groups. We think that especially halofuginone is a drug that can be used safely to prevent fibrosis due to radiotherapy, but further studies are needed.

摘要

在这项研究中,我们评估了卤夫酮和甲基强的松龙对大鼠头颈部放疗后可能发生的下咽和食管狭窄的影响。大鼠随机分为四组,除对照组外,所有大鼠的头颈部均给予 18Gy 照射。第 1 组(对照组):未给予放射治疗或药物治疗。第 2 组(放射组):仅给予放射治疗,无任何药物。第 3 组(卤夫酮组):每天腹腔内给予卤夫酮 100μg/kg。第 4 组(甲基强的松龙组):每天肌肉注射甲基强的松龙 1mg/kg。所有组大鼠在照射后 90 天,用光镜观察近端食管和下咽的纤维化、成纤维细胞增殖、血管生成、上皮异型性、坏死、多形核白细胞、单核细胞和狭窄指数,并通过生物化学方法评估羟脯氨酸水平。与对照组相比,放射组的纤维化、上皮异型性和羟脯氨酸水平明显升高(P<0.05)。我们在卤夫酮组或对照组中均未观察到纤维化。与放射组相比,甲基强的松龙组的纤维化也明显降低(P<0.05)。各组狭窄指数评分的差异无统计学意义(P<0.05)。各组血管生成相似。我们认为,特别是卤夫酮是一种可安全用于预防放疗引起的纤维化的药物,但需要进一步研究。

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本文引用的文献

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The effect of halofuginone, a specific inhibitor of collagen type 1 synthesis, in the prevention of esophageal strictures related to caustic injury.卤夫酮(一种Ⅰ型胶原蛋白合成的特异性抑制剂)在预防与腐蚀性损伤相关的食管狭窄中的作用。
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Am J Surg. 2004 Feb;187(2):257-60. doi: 10.1016/j.amjsurg.2003.11.008.
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Amelioration of radiation-induced fibrosis: inhibition of transforming growth factor-beta signaling by halofuginone.辐射诱导纤维化的改善:卤夫酮对转化生长因子-β信号传导的抑制作用
J Biol Chem. 2004 Apr 9;279(15):15167-76. doi: 10.1074/jbc.M309798200. Epub 2004 Jan 19.
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Stricture of the proximal esophagus in head and neck carcinoma patients after radiotherapy.头颈部癌患者放疗后近端食管狭窄
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The effects of corticosteroids and vitamin A on the healing of tracheal anastomoses.皮质类固醇和维生素A对气管吻合口愈合的影响。
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Halofuginone, an inhibitor of type-I collagen synthesis and skin sclerosis, blocks transforming-growth-factor-beta-mediated Smad3 activation in fibroblasts.常山酮是I型胶原蛋白合成和皮肤硬化的抑制剂,可阻断成纤维细胞中转化生长因子-β介导的Smad3激活。
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